QUESTIONNAIRES

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The 4^th week witnesses the differentiation of the cranial part of the neural tube into the 3 brain vesicles. Boundary demarcation follows differential growth rate leading to the formation of the prosencephalon, mesencephalon and rhombencephalon cranio-caudally. Same mechanism results in the formation of 2 flexures, cervical and cephalic flexures. Cephalic flexure opens to the ventral surface while the cervical opens to the dorsal surface.

By the 5th week of development, the Prosencephalon is divided into the Telencephalon and Diencephalon by differential growth rate. The Rhombencephalon also divides into the cranial Metencephalon and caudal Myelencephalon roughly by the cephalic (Pontine) flexure. The canal of the neural tube follows the differentiation leading to formation of Lateral, 3rd, 4th ventricles and the Aqueduct of Sylvius.

Telencephalon

The prosencephalon undergoes massive growth in the 5th week. Growth is more in the cranio-lateral portion as against the midline portion. The differential growth rate results in the ballooning of the lateral portion forming the telencephalon while the more quiescent midline portion forms the diencephalon. Ballooning is more in the dorsal part of the telencephalon, the ventral part consist largely of the corpus striatum.

The roof plate ependymal layers in addition to surrounding vascular mesenchyme form the choroid plexus.

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The choroid plexus bearing portion get “invaginated” due to the lateral expansion of the ballooning lateral wall.

Just beyond the choroid plexus bearing region, there is proliferation of neuroblast resulting in the slightly thickened portion that forms the Hippocampus. The hippocampal portion get “buried” within the enlarging cortex alongside the roof portion. It bulges into the cavity of the lateral ventricle. The enlarging dorsal portion of the telencephalon forms the cerebral cortex. Expansion is in the anterior, posterior and lateral directions forming the frontal, occipital and temporal lobes respectively. The ballooned cerebral cortex envelopes the diencephalon, mesencephalon and upper part of metencephalon.

Axons from the cortical neurons coalesce and pass through the corpus striatum dividing it into the medial caudate nucleus and the lateral lentiform nucleus. The dividing axonal bundle forms the internal capsule.

In the latter quarter of gestation, expansion of the cerebral cortex exceeds the capacity of the cranial vault resulting in convolutions.

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The degree of convolutions is directly related to the degree of behavioural and neuronal complexity.

Diencephalon

The portion of the prosencephalon just caudal and medial to the telencephalon. It consists of roof plate and 2 alar plate, basal plate and floor plate are absent. The roof plate consists of ependymal lining which forms the choroid plexus with the surrounding vascular mesenchyme.

There is a caudal neuroepithelial thickening on the dorsal surface which evaginates around the 7^th week to form the pineal body sitting on the mesencephalon.

The alar plate witness aggregation of cells which is divided into a dorsal thalamus and a ventral hypothalamus by a hypothalamic sulcus. Cells of the thalamus proliferate very rapidly resulting in an inward bulge of the Thalamus obliterating the cavity and forming an adhesion. A ventral thickening of the neuroepithelium results in the formation of the mammillary body which is functionally related to the hypothalamus. An extension of the ventral wall forms the infundibulum. The infundibulum alongside the Rathke’s pouch (from the oral cavity) form the pituitary gland sitting in the Sella Turcica. The cephalic flexure topographically makes the connection possible.

Mesencephalon

It has the typical basal and alar portions, the basal (ventral) part mediate motor functions while the alar (dorsal) part mediates sensory function.

The sulcus limitans forms the boundary between the 2 sides. The basal plate contains 2 groups of motor cells that aggregate into nuclei viz;

Somatic efferent; medially placed CN3 and CN4 motor supply to the extraocular muscles.

General visceral efferent; laterally placed nucleus of Edinger-Westphal (sphincter pupillary muscle).

Fibers that connect the spinal cord through the pons from the cerebral cortex pass through the marginal layer over the basal layer. Marginal layer over the basal layer enlarges to accommodate fibers forming the crus cerebri. No particular nucleus is formed in the alar plate of the mesencephalon. The overlying marginal layer of the alar plate had neuroblast wave in it resulting in its enlargement. Initially 2 longitudinal elevation is noticed in the marginal layer of the alar plate, with further development, a transverse furrow separates them. 4 colliculi are thus formed namely the inferior and superior colliculi on both sides of the median sulcus. Serve as synaptic relay centre for auditory and visual impulses respectively.

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Metencephalon

It is the cranial portion of the Rhombencephalon. It has well defined basal and alar plate in which neuroblasts form cellular aggregates that form nuclei. The roof plate consists largely of ependymal layer, opened alar plate. It is also the point of formation of the pons and cerebellum.

The fibres from the cerebral cortex to the spinal cord pass through the marginal layer that overlies the basal plate. Passage of the fibres result in the enlargement of the marginal layer forming the Pons. In addition to the fibres, pontine nuclei that are formed from the alar region of the rhombencephalon migrate in the marginal layer into the Pons. The basal plate neuroblast differentiate into neurons that are arranged into 3 motor nuclei mediolaterally;

Somatic efferent; CN6 for extraocular mm,

Special visceral efferent; CN5, CN7 for the 1^st and 2^nd pharyngeal arches.

General visceral efferent; CN9 secretomotor supply submandibular and sublingual glands

The alar plate of the metencephalon contains 3 groups of nuclei that subserve sensory modalities;

Somatic afferent; CN5, CN8 complex

The dorsolateral part of the marginal layer over the alar plate differentiates into the Rhombic lip.

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The rhombic lip is wide apart caudally but closes cranially. Pontine flexure ensures the folding of the metencephalon on itself while the rhombic lip differentiates into the cerebellar plates. At 12 weeks, a central vermis and 2 lateral dilated cerebellar hemisphere are identified.

A transverse fissure separates the cerebellar plate into an upper and lower parts. The fissure separate the vermis from the Nodule while the hemisphere is separated from the Flocculus.The developing cerebellum consist of 3 layers viz; neuroepithelial, mantle and marginal. The external granular layer differentiates from the neuroepithelial layer. The EGL give rise to granule, purkinje, golgi II neuron cells by the 6^th month, while the other cells (basket and stellate) are derived from the marginal layer

Myelencephalon

This is the caudal portion of the rhombencephalon. The dorso-lateral wall is opened up, basal and alar plate are still identifiable separated by the sulcus limitan. 3 set of motor nuclei are identified in the basal plate;

Somatic efferent; forms a motor column continuous cranio-caudally, CN12, (tongue) CN6, CN4, CN3 (eye) at different levels.

Special visceral efferent; continues cranially as a motor column CN11, CN10, CN9 supplying the striated muscles of the soft palate and larynx, pharynx, heart and gut.

General visceral efferent; supply the involuntary muscle of the gut, heart and respiratory system.

The alar plate have similar arrangement;

Somatic afferent; CN8, CN5 for the ear and head surface.

Special visceral afferent; CN9 for the tongue taste bud.

The ependymal lining of the roof plate alongside the vascular mesenchyme form the choroid plexus that produces CSF.

NEUROEPITHELIAL CELLS

The neuroepithelial cells lining the neural tube are of simple columnar type.

Increase cellular proliferation after closure of tube, giving rise to neuroblast (large deeply stained nucleus and pale cytoplasm). The neuroblast gives rise to the 2^nd layer, mantle layer which differentiate

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into the gray matter. The axons of the mantle layer neurons coalesce in the 3^rd layer (outermost) forming the marginal layer.

The mantle layer differentiates into a basal and alar plate.

The roof and floor plate are usually devoid of neuroblast, have only the ependymal layer.

The ependymal layer is the final derivative of the neuroepithelial layer.

The dorsal Alar plate houses neurons that subserve sensory modalities, while the ventral basal plate houses neurons that subserve motor modalities.

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NEUROHISTOLOGY

Neuroblast; derived from neuroepithelial cell, differentiate through uni, bi to multipolar neurons. Neurons may take different shapes and size depending on function.

Glial cell; produced by the neuroepithelial cells following the production of neurons. Differentiate into astrocyte in the mantle layer and oligodendrocyte in the marginal layer.

Astrocytes are star shaped, mainly protoplasmic in the mantle layer and fibrous in the marginal layer. It is important for the formation of the blood brain barrier.

Oligodendrocytes have small round deeply stained nucleus usually with a halo in routine stain, appear in pair or string like formation. It is responsible for myelination in the central nervous system. Myelination of the white matter begins in the 2^nd trimester and continues postnatally.

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Microglia are of mesenchymal origin, invade the CNS in the latter half of gestation. Usually cigar shaped with fine processes. They are phagocytic cells

Ependymal cells are the final derivative of neuroepithelial cells. They line the ventricle and central canal. They are cuboidal and low columnar in shape.

SPINAL CORD

The mantle layer gives rise to the gray matter of the spinal cord, while the marginal layer forms the white matter of the spinal cord. Ventral basal plate subserves motor function while dorsal alar plate subserves sensory functions. Neuroblast aggregation in between the basal and alar plate for the intermediate horn in some part of the developing spinal cord. Intermediate horn neuroblast differentiates into the neurons of the sympathetic portion of the autonomic nervous system. Intermediate horn is limited to the region of T1 to T12 and L2-L3.

The axons of the basal plate neuron coalesce exiting through the marginal layer to form the ventral motor root of the corresponding spinal nerve about the 4th week. Dorsal root ganglia are derivatives of the neural crest cells, its neuroblast differentiate into bipolar neurons.

The medial process enters the marginal layer of the alar plate of the SC ending in the dorsal horn or ascending to higher centers. The other process that grows peripherally coalesces with the ventral motor root to form the spinal nerve trunk. Myelination is a function of the Schwann cells in the axons outside the SC while the portion within the SC is myelinated by oligodendrocyte.

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The rate of elongation of the spinal cord and the vertebral column is not the same. The vertebral column outpaces the spinal cord resulting in an apparent ascent of the developing spinal cord. At about 3^rd month of life, spinal cord extends the entire length of the vertebral column, at birth spinal cord ends at the lower border of L3 while at adult hood it ends at L2/L3 boundary. Implication is the obliquity of spinal nerve forming cauda equine and the formation of filum terminale.

NEURONAL MIGRATION

The neuroblast of the cerebral cortex proliferates rapidly around the ventricle, forming neurons and supporting (glia) cells. The glial cells differentiate into the oligodendrocyte and astrocyte.

The neurons that are formed from the neuroblast are largely of 2 types;

viz granular (sensory cortex) and pyramidal (motor). Different sizes and

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composition of neurons at each point confer a stratified arrangement on the cerebral cortex. Each layer consists of neurons of specified composition and subserves similar functions. Movement of forming neurons from the point of neuroblast proliferation to their definitive position is mediated by internal and external cues.

Mechanism of migration is either radial or tangential means. While radial migration means is mainly employed by the granular and pyramidal neurons, the tangential mean is employed by interneurons.

Settling of the neuron in their definitive position is in an inside-out fashion. Migration results in 6-layered cortical arrangement.

• Molecular; few oligodendrocyte almost no neuron.

• External granular; more of round granular neurons.

• External pyramidal; contains small pyramidal neurons.

• Internal granular; contain granular cells that are closely packed.

• Internal pyramidal; contain medium to large pyramidal cells, home to Betz cells.

• Multiform layer; contains different cell type.

Clinical correlates

Anencephaly - this is the absence of a major portion of the brain, skull and scalp that occurs during embryonic r. It is a cephalic disorder that results from a neural tube defect that occurs when the rostral(head) end of the neural tube fails to close, usually between the 23^rd and 26^th day of conception. With very few exceptions, infants with this disorder do not survive longer than a few hours or possibly days after birth.

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Spina bifida - this is a developmental congenital disorder caused by the incomplete closing of the embryonic neural tube. Some vertebrae overlying the spinal cord are not fully formed and remain unfused and open. If the opening is large enough, this allows a portion of the spinal cord to protrude through the opening in the bones. There may or may not be a fluid – filled sac surrounding the spinal cord. Spinal bifida malformations fall into three categories: spina bifida occulta, spina bifida cystic with meningocele, and spina bifida cystic with myelomeningocele. The most common location of the malformations is the lumbar and sacral areas. Spina bifida can be surgically closed after birth, but this does not restore normal function to the affected part of the spinal cord.

4.0 SUMMARY

• The CNS is an ectodermal derivative that begins to differentiate in the 3^rd intrauterine week in humans.

• The first indication of the nervous system is within the neural plate, a thickened area of the ectoderm that forms after the ovum has been fertilised in the third week of gestation.

• The neural plate thickens rostral to the primitive node and midline depression in the neural plate forms the neural groove.

Edges of the neural groove rise on both sides of the midline, fusing to convert the groove to a tube. The neural tube is the beginning of the brain and spinal cord. As the neural tube separates from the surface ectoderm cells, the neural folds form the neural crest. Ganglia of the spine, cranial and autonomic nervous system develop from the neural crest.

• Anomalies of the closure of the neural tube results in several clinical conditions such as anencephaly and spinal bifida.

• The 4^th week witnesses the differentiation of the cranial part of the neural tube into the 3 brain vesicles which leads to the formation of the prosencephalon, mesencephalon and rhombencephalon cranio-caudally. Same mechanism results in the formation of 2 flexures, cervical and cephalic flexures.

Cephalic flexure opens to the ventral surface while the cervical opens t the dorsal surface.

• By the 5th week of development, the Prosencephalon is divided into the Telencephalon and Diencephalon by differential growth rate. The Rhombencephalon also divides into the cranial Metencephalon and caudal Myelencephalon roughly by the cephalic (Pontine) flexure.

• The neuroblast of the cerebral cortex proliferates rapidly around the ventricle, forming neurons and supporting (glia) cells. The glial cells differentiate into the oligodendrocyte and astrocyte.

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SELF – ASSESSMENT EXERCISE

i. What is the neural plate?

ii. What are the differences between the right and left hemispheres of the brain?

iii. What are the primitive general functional areas of the brain?

iv. When do the fontanelles of the skull close?

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UNIT 2 CEREBRAL HEMISPHERE